Hutsell Blake A, Negus S Stevens, Banks Matthew L
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA; Institute for Drug and Alcohol Abuse Studies, Virginia Commonwealth University, Richmond, VA, USA.
Drug Alcohol Depend. 2015 Jan 1;146:52-60. doi: 10.1016/j.drugalcdep.2014.11.003. Epub 2014 Nov 20.
We have previously demonstrated reductions in cocaine choice produced by either continuous 14-day phendimetrazine and d-amphetamine treatment or removing cocaine availability under a cocaine vs. food choice procedure in rhesus monkeys. The aim of the present investigation was to apply the concatenated generalized matching law (GML) to cocaine vs. food choice dose-effect functions incorporating sensitivity to both the relative magnitude and price of each reinforcer. Our goal was to determine potential behavioral mechanisms underlying pharmacological treatment efficacy to decrease cocaine choice.
A multi-model comparison approach was used to characterize dose- and time-course effects of both pharmacological and environmental manipulations on sensitivity to reinforcement.
GML models provided an excellent fit of the cocaine choice dose-effect functions in individual monkeys. Reductions in cocaine choice by both pharmacological and environmental manipulations were principally produced by systematic decreases in sensitivity to reinforcer price and non-systematic changes in sensitivity to reinforcer magnitude.
The modeling approach used provides a theoretical link between the experimental analysis of choice and pharmacological treatments being evaluated as candidate 'agonist-based' medications for cocaine addiction. The analysis suggests that monoamine releaser treatment efficacy to decrease cocaine choice was mediated by selectively increasing the relative price of cocaine. Overall, the net behavioral effect of these pharmacological treatments was to increase substitutability of food pellets, a nondrug reinforcer, for cocaine.
我们之前已经证明,在恒河猴的可卡因与食物选择程序中,连续14天使用苯双甲吗啉和右旋苯丙胺治疗或去除可卡因可得性,均可减少对可卡因的选择。本研究的目的是将串联广义匹配定律(GML)应用于可卡因与食物选择的剂量效应函数,该函数要考虑到对每种强化物的相对量值和价格的敏感性。我们的目标是确定药物治疗降低可卡因选择的潜在行为机制。
采用多模型比较方法来描述药物和环境操作对强化敏感性的剂量和时间过程效应。
GML模型很好地拟合了个体猴子的可卡因选择剂量效应函数。药物和环境操作导致的可卡因选择减少,主要是由于对强化物价格的敏感性系统性降低以及对强化物量值的敏感性非系统性变化。
所采用的建模方法在选择的实验分析与作为可卡因成瘾候选“基于激动剂”药物进行评估的药物治疗之间提供了理论联系。分析表明,单胺释放剂减少可卡因选择的治疗效果是通过选择性提高可卡因的相对价格来介导的。总体而言,这些药物治疗的净行为效应是增加食物颗粒(一种非药物强化物)对可卡因的可替代性。